Previous clinical and pre-clinical studies have shown that the dysregulation in dopamine transmission plays a criticial role in substance abuse. The studies presented in this application include the candidate's work characterizing the alteration in dopamine transmission seen in addiction. These studies include research done in cocaine, alcohol, and heroin dependence, and show that each of these disorders is associated with a loss of D2/3 receptor binding and pre-synaptic dopamine transmission. Importantly, the work done in cocaine dependence shows that dopamine transmission is predictive of relapse. The next step is to explore the mechanisms that contribute to dopamine dysregulation in addition to studying other neurotransmitter systems that directly regulate dopamine transmission. These studies include imaging micriglial activation, in addition to the kappa and neurotensin receptors systems. The candidate developed her PET imaging career through the K23 award mechanism. Due to the support provided by that award, she was able to pursue a career in imaging studies in substance dependent populations. As an independent researcher, the candidate has continued this line of work. In addition, the candidate has pursued numerous collaborations in an effort to bring PET radioligand imaging into more types of clinical research. This application for a K02 awardwill allow the candiate's career to continue unbinterupted as she pursues new directions in PET imaging. RELEVANCE (See instructions): Previous work performed by the applicant for this award have shown that dopamine is involved in drug addiction. The next set of studies will examine the cause of the changes in brain dopamine and ways to correct this deficit.